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Cardiovascular magnetic resonance in children with suspected myocarditis: current practice and applicability of adult protocols

Published online by Cambridge University Press:  24 January 2022

Barbara Pitak
Affiliation:
Department of Congenital Heart Disease and Pediatric Cardiology, German Heart Center Berlin, Berlin, Germany
Bernd Opgen-Rhein
Affiliation:
Department of Pediatrics, Division Cardiology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Stephan Schubert
Affiliation:
Department of Congenital Heart Disease and Pediatric Cardiology, German Heart Center Berlin, Berlin, Germany DZKH (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany Center for Congenital Heart Disease/Pediatric Cardiology, Heart and Diabetes Center NRW, University Clinic of Ruhr University Bochum, Bad Oeynhausen, Germany
Katja Reineker
Affiliation:
Department of Pediatric Cardiology, Universitäts-Herzzentrum Freiburg Bad Krozingen, Freiburg, Germany
Gesa Wiegand
Affiliation:
Department of Pediatric Cardiology, University Hospital Tübingen, Tübingen, Germany
Dorothée Boecker
Affiliation:
Department of Pediatric Cardiology, University Hospital Erlangen, Erlangen, Germany
Axel Rentzsch
Affiliation:
Department of Pediatric Cardiology, Universitätsklinikum des Saarlandes, Homburg, Germany
Bettina Ruf
Affiliation:
Department of Pediatric Cardiology, German Heart Center Munich, Munich, Germany
Sevinc Özcan
Affiliation:
Department of Pediatric Cardiology, Uniklinik RWTH Aachen, Aachen, Germany
Bardo Wannenmacher
Affiliation:
Department of Pediatric Cardiology, Heart Center Leipzig, Leipzig, Germany
Thomas Pickardt
Affiliation:
Competence Network for Congenital Heart Defects, Berlin, Germany
Franziska Seidel*
Affiliation:
Department of Congenital Heart Disease and Pediatric Cardiology, German Heart Center Berlin, Berlin, Germany Department of Pediatrics, Division Cardiology, Charité-Universitätsmedizin Berlin, Berlin, Germany DZKH (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany Institute of Cardiovascular Computer-assisted Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany Experimental & Clinical Research Center, a cooperation between the Max-Delbrück Center for Molecular Medicine in the Helmholtz Association & Charité – Universitätsmedizin Berlin, Berlin, Germany
Daniel Messroghli
Affiliation:
DZKH (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany Department of Internal Medicine and Cardiology, German Heart Center Berlin, Berlin, Germany Medical Department, Division of Cardiology, Charité – Universitätsmedizin Berlin, Berlin, Germany
*
Author for correspondence: Dr. Franziska Seidel, Department of Congenital Heart Disease and Pediatric Cardiology, German Heart Center Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Tel: (+49) 30 4593-2800. E-mail: seidel@dhzb.de
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Abstract

Background:

Cardiovascular magnetic resonance serves as a useful tool in diagnosing myocarditis. Current adult protocols are yet to be validated for children; thus, it remains unclear if the methods used can be applied with sufficient image quality in children. This study assesses the use of cardiovascular magnetic resonance in children with suspected myocarditis.

Methods:

Image data from clinical cardiovascular magnetic resonance studies performed in children enrolled in Mykke between June 2014 and April 2019 were collected and analysed. The quality of the data sets was evaluated using a four-point quality scale (4: excellent, 3: good, 2: moderate, 1: non-diagnostic).

Results:

A total of 102 patients from 9 centres were included with a median age (interquartile range) of 15.4(10.7-16.6) years, 137 cardiovascular magnetic resonance studies were analysed. Diagnostic image quality was found in 95%. Examination protocols were consistent with the original Lake Louise criteria in 58% and with the revised criteria in 35%. Older patients presented with better image quality, with the best picture quality in the oldest age group (13-18 years). Sedation showed a negative impact on image quality in late gadolinium enhancement and oedema sequences. No such correlation was seen in cardiac function assessment sequences. In contrast to initial scans, in follow-up examinations, the use of parametric mapping increased while late gadolinium enhancement and oedema sequences decreased.

Conclusion:

Cardiovascular magnetic resonance protocols for the assessment of adult myocarditis can be applied to children without significant constraints in image quality. Given the lack of specific recommendations for children, cardiovascular magnetic resonance protocols should follow recent recommendations for adult cardiovascular magnetic resonance.

Type
Original Article
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2022. Published by Cambridge University Press

Myocarditis is an important cause of morbidity and mortality in children and young adults, carrying a significant risk for the development of acute or chronic heart failure. Reference Kindermann, Barth and Mahfoud1Reference Towbin, Lowe and Colan4 According to a recent study by Martins et al., only less than every third paediatric patient diagnosed with myocarditis recovers completely. Reference Martins, Ait-Ali and Khraiche5 The variety and non-specificity of symptoms as well as its similarity to acute coronary syndrome may delay correct clinical and therapeutic decisions in patients with myocarditis. These symptoms include chest pain, dyspnoea, fatigue, and ventricular arrhythmia. Reference Kern, Modi, Atalay and Kochilas6 The clinical diagnosis can be supported by several diagnostic tools. However, due to their poor sensitivity and specificity in detecting a myocarditis, no single diagnostic tool is definitive in confirming or ruling out a diagnosis. Reference Caforio, Pankuweit and Arbustini7 The gold standard is the endomyocardial biopsy, an invasive diagnostic tool with a considerable risk for complications. Its diagnostic validity may be impaired by sampling errors and high inter-observer variability in tissue interpretation. Reference Aretz8,Reference Baughman9 Moreover, the typical distribution of changes in myocarditis is subepicardial and intramural – areas that are often inaccessible for endomyocardial biopsy. Reference Martins, Ait-Ali and Khraiche5,Reference Mahrholdt, Wagner and Deluigi10,Reference Raimondi, Iserin and Raisky11 Thus, the most promising non-invasive approach – cardiovascular magnetic resonance – has attracted more and more interest in recent years. In adults, cardiovascular magnetic resonance has been proven to be a useful tool for diagnosing myocarditis. Reference Bozkurt, Colvin and Cook12 Furthermore, in children with myocarditis and newly diagnosed dilated cardiomyopathy MRI has shown a predictive value of cardiac recovery. Reference Martins, Ait-Ali and Khraiche5,Reference Raimondi, Iserin and Raisky11,Reference Ait-Ali, Martins and Khraiche13 A first attempt at standardising cardiovascular MRI in adults with acute myocarditis was made in 2009 by the Lake Louise Criteria, where T1- and T2-based methods were combined for comprehensive tissue characterisation. Reference Friedrich, Sechtem and Schulz-Menger14 An updated version of these criteria based on more recent cardiovascular magnetic resonance acquisition techniques was published in 2018. Reference Ferreira, Schulz-Menger and Holmvang15 In children, the use of cardiovascular magnetic resonance for detecting myocarditis was first described in 1991. Reference Gagliardi, Bevilacqua, Di Renzi, Picardo, Passariello and Marcelletti16 The method has continued to gain popularity ever since. A more recent paediatric study conducted on a large cohort of patients with myocarditis over a period of time from 2006 to 2011 found an increase in usage of cardiovascular magnetic resonance by almost 23%. Reference Ghelani, Spaeder, Pastor, Spurney and Klugman17 The society for cardiovascular magnetic resonance recommendation for scanning patients with a COVID infection embraces inclusion of parametric mapping to imaging protocols in children and adults. Reference Kelle, Bucciarelli-Ducci and Judd18 Nevertheless, in contrast to adults, the use of cardiovascular magnetic resonance for determining myocarditis in children has not been validated systematically, and standardised diagnostic guidelines and clinical protocols are still lacking. Besides the smaller total number of cases, additional diagnostic challenges in the paediatric group of patients include physiological aspects such as high heart rates, smaller anatomy, and limited compliance. As there are only a few contemporary paediatric studies, data regarding the use of cardiovascular magnetic resonance in children are still very limited. In particular, it remains unclear if the methods that are used in adult cardiovascular magnetic resonance can be applied with sufficient image quality in children, which is a prerequisite of their meaningful use for diagnostic purposes. Reference Sachdeva, Song, Dham, Heath and DeBiasi19Reference Liu, Yang, Su, Xu and Wen21 .

The aim of this study was to assess the German use of cardiovascular magnetic resonance in a cohort of children with suspected myocarditis. We specifically investigated imaging protocols and image quality. Our study includes the review of selected acquisition parameters used in parametric mapping.

Materials and methods

Patient selection and data collection

This study is a subanalysis from Mykke – a prospective multicenter registry for children and adolescents with suspected myocarditis (ClinicalTrials.gov Identifier: NCT02590341) collecting data on clinical courses, diagnostics, and therapy. Reference Messroghli, Pickardt and Fischer22 Ethical approval was first obtained at the initiating centre (German Heart Center Berlin, Germany) from the ethics committee of Charité Universitätsmedizin Berlin and subsequently confirmed by the local authorities of all collaborating centres (ID EA2/074/13). Within the MYKKE registry, patient data are entered in an online database, hosted by the Competence Network for Congenital Heart Defects, Germany. Image data from clinical cardiovascular magnetic resonance studies performed in children enrolled in Mykke between June 2014 and April 2019 were collected on a central image server at the coordinating centre and analysed for this study. The inclusion criteria were as follows: age <18 years old and clinically suspected myocarditis. All patients or their legal guardians provided written informed consent. The indication for cardiovascular magnetic resonance was set by the referring physician. Demographic data and basic functional and volumetric cardiovascular magnetic resonance analysis were extracted from the registry database. Patients were divided into 3 groups according to their age at the time of cardiovascular magnetic resonance (0-1, 2-12, 13-18 years). Reference Messroghli, Pickardt and Fischer22

Cardiovascular magnetic resonance image analysis

Data analysis and interpretation were performed at the coordinating centre by two independent clinicians (2 and 5 years of experience in cardiac imaging, respectively). In case of discrepancies, a joined reading was performed and a consensus was agreed upon. Visual (qualitative) analysis was done for balanced steady state free precession cine images, T2-weighted, short tau triple inversion recovery and turbo-spin-echo imaging, late gadolinium enhancement, phase-sensitive inversion recovery as well as for T1 and T2 mapping. The quality of each data set was evaluated using a four-point quality scale, similar to a previous study of Monti et al. Reference Monti, Codari and Cozzi23 : a score of 4 indicated excellent image quality with artefacts not affecting the heart, 3 – good image quality with minor involvement of the heart, 2 – moderate image quality with severe artefacts and a score of 1 non-diagnostic. In scans with image quality >”1,” the image quality would be sufficient to enable using the scan in the diagnostic process. The use of T1-weighted turbo-spin-echo, early gadolinium enhancement imaging, and magnetic resonance angiography was examined without the application of quality scale. The MRI image analysis was carried out using Horos medical image viewer (Nimble Co. LLC d/b/a Purview, Annapolis, MD USA).

Statistical analysis

Categorical variables are summarised by frequencies and percentages. For continuous measures, data are presented as median values and interquartile ranges. Pearson’s chi-square test and Fisher`s exact test were used to compare dichotomous variables. For comparison of independent groups, Mann–Whitney U and Kruskal–Wallis tests were applied. A probability value of <0.05 was considered statistically significant. Data were analysed with IBM Corp. SPSS Version 24.0 (Armonk, NY, USA).

Results

Demographics

A total of 102 patients from 9 centres with a clinically suspected myocarditis were included in the study between June 2014 and April 2019. The youngest age group (0-1 years) consisted of 10 patients, the middle age group (2-12 years) of 31 patients and the oldest age group (13-18 years) of 96 patients. The median age was 15.4 (interquartile range 10.7-16.6) years with a body surface area of 1.7 (1.2-1.9) m2, and 71% were male. The time from admission to cardiovascular magnetic resonance was 8.0 (4.0-20.3) days. A follow-up cardiovascular magnetic resonance was available in 35 patients. Patient characteristics and basic MRI findings are listed in Table 1.

Table 1. Demographics and basic CMR findings

Values are n (%) or median (interquartile range). CMR: cardiovascular magnetic resonance, LVEF: left ventricular ejection fraction, LVEDV: left ventricular end-diastolic volume.

cardiovascular magnetic resonance sequences

Cardiovascular magnetic resonance was performed in 96% using a 1.5 T system (Siemens Healthcare, Erlangen, Germany; Philips, Best, The Netherlands; Genesis Signa, General Electric Medical Systems, Milwaukee, WI, USA). A 3 T system (Siemens Healthcare, Erlangen, Germany) was used in 4% of the examinations. Four per cent of the scans were done under general anaesthesia, 8% under deep conscious sedation with use of free-breathing sequences, and 88% without any sedation. Table 2 presents an overview of the performed sequences at initial and follow-up examinations. The initial protocol included sequences assessing cardiac function, combined with late gadolinium enhancement applied in 99%, and oedema imaging in 82%. Late gadolinium enhancement standard 2 D, standard 3 D and phase-sensitive inversion recovery sequences were used. In addition, mDixon and FLASH sequences were used – however, their image quality was not evaluated using the 4-point scale. In the baseline as well as the follow-up MRI, the use of the 3 D sequences was more frequent. The image quality of the scans using 3 D sequences was better than the ones using 2 D sequences (in the 3 D technique 35.3 % of the scans presented an excellent image quality, whereas in the 2 D technique 31.5 % of the scans displayed an excellent image quality. T1 mapping (pre- and/or post-contrast) was performed in 74% of the examinations and T2 mapping in 28%. Sixty per cent of scans included early gadolinium enhancement. In the follow-up examinations we observed an increase in the use of parametric mapping – T1 native by 13% (p = 0.22), post-contrast by 8% (p = 0.44) and T2 by 17% (p = 0.09). Nevertheless, there was a decrease in the use of T2-weighted imaging (by 5%, p = 0.61), early gadolinium enhancement (by 11%, p = 0.32) and late gadolinium enhancement (by 2%, p = 0.44). In 58% (80/137) of the data sets, the applied examination protocol was consistent with the original Lake Louise Criteria. Thirty-five per cent (48/137) of the data sets used an examination protocol that was compatible with the revised version of the Lake Louise Criteria. Respectively, according to the original Lake Louise Criteria, 42% of the scans were incomplete. According to the revised Lake Louise Criteria, 65% of the scans were incomplete.

Table 2. CMR sequences performed at initial and follow-up CMR

Values are given in n and %. CMR: Cardiovascular Magnetic Resonance, 2CH: 2 Chamber view, 4CH: 4 Chamber view, 3CH: 3 Chamber view, SAX: Short Axis view, bSSFP: Balanced Steady State Free Precession, STIR: Short Tau Inversion Recovery, PSIR: Phase-Sensitive Inversion Recovery, MOLLI: Modified Look-Locker inversion recovery, SASHA: Saturation recovery single-shot acquisition, ECV: Extracellular volume, GraSE: Gradient and Spin-Echo.

Image quality

Table 3 lists the findings on image quality for the different sequences. Image quality ranged from excellent to non-diagnostic. Exemplary gradings of all the sequences analysed are illustrated in Figure 5. A diagnostic image quality was found in 95% of the analysed data sets. Ninety-eight per cent of Cine scans had diagnostic image quality, among them 34% with an excellent image quality. Twenty-seven per cent (30/111) of oedema sequences were graded as excellent and 9% as not non-diagnostic. The T2-weighted scans performed under conscious sedation were respiratory-gated, the late gadolinium enhancement scans were not. The late gadolinium enhancement sequences were performed in the SENSE technique in order to improve the resolution and the signal-to-noise ratio. Among the late gadolinium enhancement sequences, the best overall picture quality was seen in phase-sensitive inversion recovery images with 40% excellent and only 6% non-diagnostic data sets. For 32% of the standard 2D data sets and 35% of the standard 3D data sets, late gadolinium enhancement image quality was graded as being excellent. The best overall image quality was noted for T1 mapping, where 46.3% of native and 37.8% of post-contrast examinations were graded as excellent. Diagnostic image quality was found in all performed post-contrast T1 maps and in 98% of native studies (Fig 1). There were no statistically significant differences in T1 mapping image quality between MOLLI 3-3-5 and MOLLI 5-3 (native: p = 0.15, post-contrast: p = 0.33) or between GE and GraSE techniques in T2 mapping (p = 0.33). The best picture quality in Cine sequences was seen in the oldest age group (13-18 years; 2 chamber view: p = 0.00, 4 chamber view: p = 0.047, 3 chamber view: p = 0.17, short-axis planes: p = 0.02; Fig 2). Exemplary findings are illustrated in Figure 3. In Cine imaging and T2 mapping, the image quality was not significantly different when comparing scans acquired with and without use of sedation (2 chamber view: p = 0.06, 4 chamber view: p = 0.79, 3 chamber view: p = 0.19, short-axis planes: p = 0.31, T2 mapping: p = 0.28). In other tissue characterisation sequences, the use of deep sedation influenced the image quality negatively (T1 mapping before the application of the contrast agent: p = 0.03, post-contrast: p = 0.01, late gadolinium enhancement 2D: p = 0.01, 3D: p = 0.00, phase-sensitive inversion recovery: p = 0.03; Fig 4).

Figure 1. T1 mapping – image quality.

Figure 2. Picture quality in relation to patient age in CINE imaging. 2CH: 2 chamber view, 4CH: 4 chamber view, 3CH: 3 chamber view, SAX: short axis view.

Figure 3. Mid-ventricular short axis slices demonstrating: CINE imaging, oedema imaging, native T1 mapping, and late gadolinium enhancement imaging for every age group, respectively (0-1 years: a, b, c, d; 2-12 years: e, f, g, h; 13-18 years: i, j, k, l).

Figure 4. Image quality in relation to sedation in late gadolinium enhancement. 2D: late gadolinium enhancement standard 2D, 3D: late gadolinium enhancement standard 3D, PSIR: phase-sensitive inversion recovery.

Figure 5. Exemplary quality gradings of all the sequences analysed. T2W: T2-weighted imaging, LGE 2D: late gadolinium enhancement standard 2 D, LGE 3D: late gadolinium enhancement standard 3D.

Table 3. Sequence quality information

Values are given in n and %. 2CH: 2 Chamber view, 4CH: 4 Chamber view, 3CH: 3 Chamber view, SAX: Short Axis view, STIR: Short Tau Inversion Recovery, PSIR: Phase-Sensitive Inversion Recovery.

Discussion

This study presents a view on the German use of cardiovascular magnetic resonance in children with suspected myocarditis, including an overview of cardiovascular magnetic resonance techniques, protocols, and of the resulting image quality in these patients. Our study showed good image quality in 95% of the children, comparable to data acquired in a study describing children undergoing pulmonary valve replacement (92% diagnostic-quality images). Reference de Alba, Molina Berganza, Brownlee, Khan and Adebo24 Furthermore, the image quality demonstrated a strong dependence on age: older patients showed better image quality, possibly due to better compliance and physiological differences such as lower heart rate and larger size of anatomical structures. The use of sedation in smaller children seems to be an important factor as it influences the scan quality in tissue characterisation sequences negatively.

The original Lake Louise criteria, combining T2 ratio, early and late gadolinium enhancement, still remain an essential tool for diagnosing acute myocardial inflammation in many centres. In our cohort, over half of the scans used a study protocol that was consistent with the original criteria, whereas a previous paediatric study on myocarditis found that the original Lake Louise Criteria were employed in only 28% of scans. Reference Banka, Robinson and Uppu25 The fact that the original criteria were used at such a high rate despite the lack of validation or standardisation studies in children underlines the lack of alternative approaches, which has been compensated for by the publication of the revised Lake Louise criteria in 2018. Reference Ferreira, Schulz-Menger and Holmvang15 The revised criteria combine conventional cardiovascular magnetic resonance and mapping techniques as markers for inflammatory myocardial injury. The new proposed cardiovascular magnetic resonance protocol consists of a “2 of 2” diagnostic target combination, including at least one positive T2-based criterion (global or regional increase of myocardial T2 relaxation time or an increased signal intensity in T2-weighted imaging) and at least one positive T1-based criterion (prolonged myocardial T1 time, increased extracellular volume, or presence of late gadolinium enhancement). Another essential modification is the absence of early gadolinium enhancement, as recent data suggested that excluding early gadolinium enhancement from the original study protocol would not substantially hamper diagnostic accuracy. Reference Ferreira, Schulz-Menger and Holmvang15,Reference Chu, Flewitt, Mikami, Vermes and Friedrich26

In adults, cardiovascular magnetic resonance mapping techniques have demonstrated their superiority over classical tissue characterisation techniques in several trials. In a study conducted by Ferreira et al., native T1 mapping showed higher diagnostic yield compared with T2-weighted and late gadolinium enhancement imaging. Reference Ferreira, Piechnik and DallʼArmellina27 In the MyoRacer Trial, T2 mapping had the highest sensitivity (73%) in patients with chronic symptoms. Reference Lurz, Luecke and Eitel28 The latter technique has also proven itself useful in ruling out active inflammation and differentiating between an acute and chronic process. Reference von Knobelsdorff-Brenkenhoff, Schuler and Doganguzel29 The gradually increasing importance of novel mapping techniques, which subsequently has led to the aforementioned revision of the Lake Louise criteria, is also reflected in our study: we found growing usage of parametric mapping in the follow-up examinations compared to the initial examinations. Parametric mapping has numerous advantages such as direct quantification of signal changes, higher signal-to-noise ratio and shorter breath holds with fewer breathing motion artefacts. Combined with the resilience to arrhythmias, parametric mapping results in more robust image quality and subsequently better diagnostic performance, as seen in our study where the majority of native and post-contrast T1 mapping sequences resulted in excellent or good picture quality. Reference Messner, Budjan and Lossnitzer30 Also Cornicelli et al. showed in a relatively small cohort of children with myocarditis a superior performance of parametric mapping techniques as compared to the original Lake Louise approach. Reference Cornicelli, Rigsby, Rychlik, Pahl and Robinson31 Similar to adult applications, care has to be taken that values of myocardial T1 and T2 are compared to reference values that were generated with the same technical setup as the patient data. Moreover, reference ranges should be matched for the age group of the patients. Nevertheless, in spite of the growing use of the parametric mapping illustrated in our study, according to the revised Lake Louise Criteria, 65% of the scans included in our analysis were incomplete. This further stresses out the urgent need for standardisation of study protocols by parallel publication of recommendations for scanning children and adults, as it was done in an society for cardiovascular magnetic resonance guideline for patients with COVID-19. Reference Kelle, Bucciarelli-Ducci and Judd18 Aside from highlighting the excellent performance of modern parametric mapping techniques in children, our study has important implications regarding the utility of deep sedation versus general anaesthesia during cardiovascular magnetic resonance in children. In the past, several studies on this subject have produced contradictory results. One study stated that cardiovascular magnetic resonance scans performed under deep sedation had substantially more motion artefacts. Reference Malviya, Voepel-Lewis, Eldevik, Rockwell, Wong and Tait32 As opposed to this, Fogel et al. published that cardiovascular magnetic resonance scans performed under conscious sedation presented with similar image quality and diagnostic yield compared to general anaesthesia. Reference Fogel, Weinberg and Parave33 Our study showed that in small children, necessitating the use of sedation for performing cardiovascular magnetic resonance, ventricular function assessment and parametric mapping in T2 technique do not significantly benefit from the use of general anaesthesia instead of deep sedation, whereas classical tissue characterisation techniques, requiring longer breath holds, resulted in better image quality under general anaesthesia. Therefore, in the future, the growing use of myocardial mapping techniques might contribute to reducing the need for general anaesthesia in small children and protecting the youngest patients from the risk of severe complications related to this procedure. Reference Dorfman, Odegard, Powell, Laussen and Geva34,Reference Kipps, Ramamoorthy, Rosenthal and Williams35

Our findings show that currently used adult cardiovascular MRI protocols for myocarditis can be applied to children without significant limitations in image quality. The excellent technical performance of parametric myocardial mapping techniques found in this paediatric cohort allows using protocols that assess the revised Lake Louise criteria. In the absence of specific recommendations for children, such protocols should be employed for paediatric myocarditis in order to increase standardisation and comparability of results.

There might be a selection bias related to cardiovascular magnetic resonance, with less severely ill patients having higher chances of undergoing cardiovascular magnetic resonance and patients with more severe illness not being sent for cardiovascular magnetic resonance. Therefore, our results might not represent the entire population of children with suspected myocarditis. In this study, we did not address the diagnostic power of cardiovascular magnetic resonance by examining its sensitivity and specificity. Furthermore, similarly to another paediatric study, the decision about performing a follow-up cardiovascular magnetic resonance was taken by the referral cardiologist according to local policies and a repeated written consent of a legal guardian was needed. Reference Raimondi, Iserin and Raisky11 As a result, only 34% of our patients received a follow-up cardiovascular magnetic resonance. This might have led to the heterogeneity of the data acquired at follow-up cardiovascular magnetic resonance.

Acknowledgement

The following researchers (“Mykke Consortium”) significantly contributed to the development and implementation of Mykke in the participating centres of this study: Felix Berger, MD (German Heart Center Berlin and Charité – Universitätsmedizin Berlin); Sven-Christian Weber, MD (Charité – Universitätsmedizin Berlin, Berlin); Sabine Klaassen, MD (Charité – Universitätsmedizin Berlin, Berlin; Experimental and Clinical Research Center (ECRC) and Max-Delbrück Center for Molecular Medicine, Berlin); Jirko Kühnisch (ECRC and Max-Delbrück Center for Molecular Medicine, Berlin); Sabine Schroeter (German Heart Center Berlin); Philipp Beerbaum, MD (Hannover Medical School); Ingo Dähnert, MD and Jacqueline Richter (Heart Centre, University of Leipzig); Sven Dittrich, MD and Joachim Mannert, MD (University Hospital Erlangen); Brigitte Stiller, MD and Nicolas C. Enriquez (University Heart Center Freiburg); Rainer Kozlik-Feldmann, MD, Götz Müller, MD and Adriana Busch (University Heart & Vascular Center Hamburg); Michael Hofbeck, MD (University Hospital Tübingen); Tobias Hecht, MD (Heart and Diabetes Center NRW, Bad Oeynhausen); Hans-Gerd Kehl, MD (University Hospital Münster); Hashim Abdul-Khaliq, MD and Sandra Pontius (Saarland University Medical Center, Homurg); Nikolaus Haas, MD (Ludwig Maximilians University of Munich); Trong Phi Lê, MD and Levent Celik, MD (Klinikum Links der Weser, Bremen); Andrea Engelhardt, MSc, Andrea Strötges-Achatz and Peter Ewert, MD (German Heart Centre Munich); Konrad Brockmeier, MD and Tobias Hannes (University Hospital Cologne); Christian Jux, MD and Anna-Eva Blank, MD (University Hospital Giessen); Christian Apitz, MD (University Hospital Ulm); Thomas Paul, MD and Yannic Wilberg, MD (University Medical Center Göttingen); Anselm Uebing, MD (University Hospital Schleswig-Holstein, Kiel); Gunter Kerst, MD and Stefan Ostermayer, MD (University Hospital RWTH Aachen); Caroline von dem Busche and Johannes Breuer, MD (University Hospital Bonn); Frank Uhlemann, MD (Olgahospital, Stuttgart); Matthias Gorenflo, MD and Wiebke Frede (University Hospital Heidelberg, Heidelberg); Ina Michel-Behnke, MD and Annette-Nicole Ivad, MD (Pediatric Heart Center, Medical University Vienna); Matthias Freund, MD (Hospital Oldenburg); Ralph Grabitz, MD and Ia Zakaraia, MD (University Hospital Halle/Saale); Ulrike Bauer, MD (Competence Network for Congenital Heart Defects, Berlin); Walter Knirsch, MD (Pediatric Heart Center, University Children’s Hospital, Zurich); Malte Frenzel, MD (University Children’s Hospital Basel); Sascha König, MD and Gleb Tarusivov, MD (Heart Center, Duisburg); Cynthia Huber and Tim Friede (Department of Medical Statistics, University Medical Center Göttingen).

Financial support

The pilot phase and scientific planning of the Mykke registry were funded through two project grants by Deutsche Herzstiftung (Frankfurt am Main, Germany). Since February 2017, Mykke has been funded by kinderherzen-Fördergemeinschaft Deutsche Kinderherzzentren e.V. (Bonn, Germany). In 2019 and 2020 there was financial support by the Berliner Sparkassenstiftung Medizin for this project. Logistic support and management of the research database are provided by the Competence Network for Congenital Heart Defects (Berlin, Germany), which received funding from The Federal Ministry of Education and Research, grant number 01GI0601 (until 2014), and the DZHK (German Centre for Cardiovascular Research) as of 2015.

Conflict of interests

No relevant financial or non-financial competing interests to report.

Ethical Standards

The authors assert that all procedures contributing to this work comply with the Helsinki Declaration of 1975, as revised in 2008, and has been approved by the institutional committees (Charité – Universitätsmedizin Berlin).

Footnotes

*

F.S. and D.M. contributed equally as Senior Authors.

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Figure 0

Table 1. Demographics and basic CMR findings

Figure 1

Table 2. CMR sequences performed at initial and follow-up CMR

Figure 2

Figure 1. T1 mapping – image quality.

Figure 3

Figure 2. Picture quality in relation to patient age in CINE imaging. 2CH: 2 chamber view, 4CH: 4 chamber view, 3CH: 3 chamber view, SAX: short axis view.

Figure 4

Figure 3. Mid-ventricular short axis slices demonstrating: CINE imaging, oedema imaging, native T1 mapping, and late gadolinium enhancement imaging for every age group, respectively (0-1 years: a, b, c, d; 2-12 years: e, f, g, h; 13-18 years: i, j, k, l).

Figure 5

Figure 4. Image quality in relation to sedation in late gadolinium enhancement. 2D: late gadolinium enhancement standard 2D, 3D: late gadolinium enhancement standard 3D, PSIR: phase-sensitive inversion recovery.

Figure 6

Figure 5. Exemplary quality gradings of all the sequences analysed. T2W: T2-weighted imaging, LGE 2D: late gadolinium enhancement standard 2 D, LGE 3D: late gadolinium enhancement standard 3D.

Figure 7

Table 3. Sequence quality information